The overall objective of the proposed research is to investigate the neurochemical mechanisms by which estradiol and progesterone control the secretion of luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary gland. This research will test the hypothesis that ovarian hormones regulate LH and PRL secretion by activating endogenous opiate peptide systems that exert localized control over the release of norepinephrine, epinephrine and serotonin. It is also hypothesized that monoaminergic control over LH and PRL is modified by the presence or absence of testosterone during a perinatal critical period. These hypotheses will be tested by the following approaches. First, ovarian hormones will be administered in specific regimens that depress or elevate LH and PRL, and the effects of these treatments on the turnover of serotonin in discrete brain nuclei will be assessed. This will identify those sites where ovarian hormones alter serotonergic activity. The second phase will attempt to establish causal relationships between the changes of serotonin activity and the changes in LH and PRL induced by the ovarian hormones. This will involve attempts to alter the expected ovarian hormonal feedback effects by producing local denervations with the neurotoxic indoleamine, 5,7-dihydroxytryptamine. The third phase will test whether ovarian hormones interact with endogenous opiate neuropeptides that influence the release of monoamines to regulate LH and PRL secretion. This will be accomplished by testing whether ovarian hormonal effects on both pituitary hormone secretion and on monoamine turnover can be affected by opiate agonists and antagonists. A fourth aspect of the project will investigate whether castration of neonatal males or administration of testosterone to neonatal females, manipulations that alter ovarian hormonal control over LH and PRL in adulthood, also alter the effects of ovarian hormones on LH-releasing hormone and on monoamine turnover.